UniProt functional annotation for Q7Z6E9



	UniProt functional annotation for Q7Z6E9

UniProt code: Q7Z6E9.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: E3 ubiquitin-protein ligase which promotes ubiquitination of YBX1, leading to its degradation by the proteasome (PubMed:18851979). May play a role as a scaffold protein to promote the assembly of the p53/TP53-MDM2 complex, resulting in increase of MDM2-mediated ubiquitination and degradation of p53/TP53; may function as negative regulator of p53/TP53, leading to both apoptosis and cell growth (By similarity). Regulates DNA-replication and the stability of chromosomal common fragile sites (CFSs) in a ZBTB38- and MCM10-dependent manner. Controls ZBTB38 protein stability and abundance via ubiquitination and proteasomal degradation, and ZBTB38 in turn negatively regulates the expression of MCM10 which plays an important role in DNA-replication (PubMed:24726359). {ECO:0000250|UniProtKB:P97868, ECO:0000269|PubMed:18851979, ECO:0000269|PubMed:24726359}.

Function: (Microbial infection) [Isoform 1]: restricts ebolavirus replication probably by impairing the vp30-NP interaction, and thus viral transcription. {ECO:0000269|PubMed:30550789}.

Catalytic activity: Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L- cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.; EC=2.3.2.27;

Pathway: Protein modification; protein ubiquitination.

Subunit: Interacts with p53/TP53 and RB1 (By similarity). Interacts also with MDM2 and YBX1 (PubMed:17470788). Interacts also with MDM2 and YBX1 (PubMed:18851979). Interacts with NEK6 (PubMed:20873783). Interacts with ZBTB38 (PubMed:24726359). {ECO:0000250|UniProtKB:P97868, ECO:0000269|PubMed:17470788, ECO:0000269|PubMed:18851979, ECO:0000269|PubMed:20873783, ECO:0000269|PubMed:24726359}.

Subunit: (Microbial infection) [Isoform 1]: Interacts with ebolavirus VP30. {ECO:0000269|PubMed:30550789}.

Subcellular location: Nucleus, nucleolus. Chromosome. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Note=Colocalizes with mitotic chromosomes. Colocalizes with NEK6 in the centrosome.

Tissue specificity: Highly expressed in the placenta and testis. Expressed at lower levels in the brain, heart, kidney, liver and lung. Overexpressed in esophageal cancer. {ECO:0000269|PubMed:15475430}.

Domain: Contains a N-terminus DWNN domain, a zinc-finger domain and a C4C4 zinc-binding RING finger domain (PubMed:22130672). The ring finger may indeed be a U-box domain (PubMed:22130672). {ECO:0000269|PubMed:22130672}.

Ptm: Phosphorylated by NEK6. {ECO:0000269|PubMed:20873783}.

Sequence caution: Sequence=AAG43155.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305}; Sequence=AAH63524.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305}; Sequence=AAL05625.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=AAL68925.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305}; Sequence=CAA59445.1; Type=Frameshift; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		E3 ubiquitin-protein ligase which promotes ubiquitination of YBX1, leading to its degradation by the proteasome (PubMed:18851979). May play a role as a scaffold protein to promote the assembly of the p53/TP53-MDM2 complex, resulting in increase of MDM2-mediated ubiquitination and degradation of p53/TP53; may function as negative regulator of p53/TP53, leading to both apoptosis and cell growth (By similarity). Regulates DNA-replication and the stability of chromosomal common fragile sites (CFSs) in a ZBTB38- and MCM10-dependent manner. Controls ZBTB38 protein stability and abundance via ubiquitination and proteasomal degradation, and ZBTB38 in turn negatively regulates the expression of MCM10 which plays an important role in DNA-replication (PubMed:24726359). {ECO:0000250\|UniProtKB:P97868, ECO:0000269\|PubMed:18851979, ECO:0000269\|PubMed:24726359}.



Function:		(Microbial infection) [Isoform 1]: restricts ebolavirus replication probably by impairing the vp30-NP interaction, and thus viral transcription. {ECO:0000269\|PubMed:30550789}.


Catalytic activity:		Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L- cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.; EC=2.3.2.27;
Pathway:		Protein modification; protein ubiquitination.
Subunit:		Interacts with p53/TP53 and RB1 (By similarity). Interacts also with MDM2 and YBX1 (PubMed:17470788). Interacts also with MDM2 and YBX1 (PubMed:18851979). Interacts with NEK6 (PubMed:20873783). Interacts with ZBTB38 (PubMed:24726359). {ECO:0000250\|UniProtKB:P97868, ECO:0000269\|PubMed:17470788, ECO:0000269\|PubMed:18851979, ECO:0000269\|PubMed:20873783, ECO:0000269\|PubMed:24726359}.
Subunit:		(Microbial infection) [Isoform 1]: Interacts with ebolavirus VP30. {ECO:0000269\|PubMed:30550789}.
Subcellular location:		Nucleus, nucleolus. Chromosome. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Note=Colocalizes with mitotic chromosomes. Colocalizes with NEK6 in the centrosome.
Tissue specificity:		Highly expressed in the placenta and testis. Expressed at lower levels in the brain, heart, kidney, liver and lung. Overexpressed in esophageal cancer. {ECO:0000269\|PubMed:15475430}.
Domain:		Contains a N-terminus DWNN domain, a zinc-finger domain and a C4C4 zinc-binding RING finger domain (PubMed:22130672). The ring finger may indeed be a U-box domain (PubMed:22130672). {ECO:0000269\|PubMed:22130672}.
Ptm:		Phosphorylated by NEK6. {ECO:0000269\|PubMed:20873783}.
Sequence caution:		Sequence=AAG43155.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305}; Sequence=AAH63524.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305}; Sequence=AAL05625.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=AAL68925.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305}; Sequence=CAA59445.1; Type=Frameshift; Evidence={ECO:0000305};